title: A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism.
abstract: Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Anne
authors.initials: A
authors.lastname: Bugge
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Mullican
authors.forename: Theresa
authors.initials: T
authors.lastname: Alenghat
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D021081:Chronobiology Disorders / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks; D002940:Circadian Rhythm; D004247:DNA / Q000378:metabolism; D044127:Epigenesis, Genetic; D005234:Fatty Liver / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015854:Up-Regulation; D000099186:Histone Deacetylase 3
chemical_list: D004247:DNA; D006655:Histone Deacetylases; D006657:Histones; D056971:Nuclear Receptor Co-Repressor 1; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D012319:RNA Polymerase II; D000099186:Histone Deacetylase 3; C539128:Ncor1 protein, mouse; C498262:Nr1d1 protein, mouse